An Emerging New Enzyme Treatment for Type 1 Gaucher Disease

In the last edition of Gauchers News, Prof Ari
Zimran, Director of the Gaucher Clinic at Shaare Zedek Medical Center in
Israel reported a new enzyme preparation for patients with Type 1 Gaucher
disease, produced by Shire Genetic Therapies. Prof Zimran provides a further
update on the results at nine months.

GA-GCB is human glucocerebrosidase which is produced in a continuous
human cell line using proprietary Gene-Activated technology. Unlike Cerezyme,
GAGCB has an identical amino acid sequence to the naturally occurring human
enzyme, which may be an advantage. This innovative technology has been used to
develop an alternative enzyme replacement therapeutic option for patients with
Gaucher disease.

'The purpose of the Phase I/II study was to assess the safety and
efficacy of GA-GCB in adult patients with Type 1 Gaucher disease. Twelve
patients received GA-GCB every other week for 9 months. Of 12 patients treated,
11 patients completed the study.

There were no drug-related serious adverse events and no patient
discontinued participation because of adverse events. Infusion related
reactions were limited, mild and transient. None of the treated patients
developed anti-GA-GCB antibodies.

The results with GA-GCB were very impressive. Notably, the GA-GCB study
did not allow children to enrol, who typically respond better to treatment, yet
similar results were obtained to the trial of Ceredase, where eight out of 12
patients were younger than 18 years of age. In the GA-GCB trial, there were
significant increases in hemoglobin (on average 2.24g/dL; mean increase of
19.2% from baseline), in platelet counts (on average 40,600/mm3; mean increase
of 67.6% from baseline) and also significant decreases in spleen and liver
volume (by 49.5% and 18.2% from baseline, respectively).

Similarly, there were significant decreases in the biomarkers
chitotriosidase (by 74.2%)and CCL18 (by 57.1%). Improvements in some parameters
were apparent as early as three months after the start of the therapy.

These results suggest that Gene-Activated humanglucocerebrosidase
(GA-GCB), holds promise as a new enzyme replacement therapy for Gaucher disease
and warrants further evaluation in clinical studies in a broader population of
patients.